Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury.

BACKGROUND: Clinically, it is well known that injury of mandibular nerve fiber induces persistent ectopic pain which can spread to a wide area of the orofacial region innervated by the uninjured trigeminal nerve branches. However, the exact mechanism of such persistent ectopic orofacial pain is not still known. The present study was undertaken to determine the role of connexin 43 in the trigeminal ganglion on mechanical hypersensitivity in rat whisker pad skin induced by inferior alveolar nerve injury. Here, we examined changes in orofacial mechanical sensitivity following inferior alveolar nerve injury. Furthermore, changes in connexin 43 expression in the trigeminal ganglion and its localization in the trigeminal ganglion were also examined. In addition, we investigated the functional significance of connexin 43 in relation to mechanical allodynia by using a selective gap junction blocker (Gap27). RESULTS: Long-lasting mechanical allodynia in the whisker pad skin and the upper eyelid skin, and activation of satellite glial cells in the trigeminal ganglion, were induced after inferior alveolar nerve injury. Connexin 43 was expressed in the activated satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin, and the connexin 43 protein expression was significantly increased after inferior alveolar nerve injury. Administration of Gap27 in the trigeminal ganglion significantly reduced satellite glial cell activation and mechanical hypersensitivity in the whisker pad skin. Moreover, the marked activation of satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin following inferior alveolar nerve injury implies that the satellite glial cell activation exerts a major influence on the excitability of nociceptive trigeminal ganglion neurons. CONCLUSIONS: These findings indicate that the propagation of satellite glial cell activation throughout the trigeminal ganglion via gap junctions, which are composed of connexin 43, plays a pivotal role in ectopic mechanical hypersensitivity in whisker pad skin following inferior alveolar nerve injury.

Roles of isolectin B4-binding afferents in colorectal mechanical nociception.

Isolectin B4-binding (IB4+) dorsal root ganglion (DRG) neurons are distinct from peptidergic DRG neurons in their terminal location in the spinal cord and respective contributions to various classes and modalities of nociception. In DRG neurons innervating the mouse colon (c-DRG neurons), the reported proportion of IB4+ population is inconsistent across studies, and little is known regarding their role in colorectal mechanonociception. To address these issues, in C57BL/6J mice, we quantified IB4+ binding after labeling c-DRG neurons with Fast Blue and examined functional consequences of ablating these neurons by IB4-conjugated saporin. Sixty-one percent of Fast Blue-labeled neurons in the L6 DRG were IB4+, and 95% of these IB4+ c-DRG neurons were peptidergic. Intrathecal administration of IB4-conjugated saporin reduced the proportion of IB4+ c-DRG neurons to 37%, which was due to the loss of c-DRG neurons showing strong to medium IB4+ intensity; c-DRG neurons with weak IB4+ intensity were spared. However, this loss altered neither nociceptive behaviors to colorectal distension nor the relative proportions of stretch-sensitive colorectal afferent classes characterized by single-fiber recordings. These findings demonstrate that more than 1 half of viscerosensory L6 c-DRG neurons in C57BL/6J mouse are IB4+ and suggest, in contrast to the reported roles of IB4+/nonpeptidergic neurons in cutaneous mechanonociception, c-DRG neurons with strong-to-medium IB4+ intensity do not play a significant role in colorectal mechanonociception.

Changes in expression of growth-associated protein-43 in trigeminal ganglion neurons and of the jaw opening reflex following inferior alveolar nerve transection in rats.

The aim of the present study was to clarify an involvement of growth-associated protein-43 (GAP-43) in the regeneration of primary afferent trigeminal ganglion (TG) neurons following inferior alveolar nerve transection (IANX). A larger number of GAP-43 immunoreactive (GAP-43 IR) TG neurons was observed in rats 3 d after IANX compared with sham rats. Growth-associated protein-43 IR TG neurons were also detected for 30 d after IANX, and the number of GAP-43 IR TG neurons was significantly higher in the IANX model until day 30. The relative number of large (>600 µm2) GAP-43 IR TG neurons was significantly lower, whereas the relative number of small (<400 µm2) GAP-43 IR TG neurons was significantly higher than that at day 0 until 30 d after IANX. To evaluate the functional recovery of damaged IAN, the jaw opening reflex (JOR), elicited by the electrical stimulation of the IAN, was measured before and after IANX. Jaw opening reflex occurrence was gradually increased and the relative threshold of electrical stimulation eliciting JOR was gradually decreased over the 30-d duration of the study. On day 30 after IANX, the JOR occurrence and relative JOR threshold were similar to those in sham rats. The present findings suggest that changes in the expression of GAP-43 in TG neurons after IANX are involved in regeneration and functional recovery of the transected IAN.

P2X3 receptor mediates ectopic mechanical allodynia with inflamed lower lip in mice.

Ectopic pain in other orofacial regions develops with local inflammation in separated orofacial structures. However, the basis for the spreading of pain to adjacent orofacial areas after local inflammation is still unknown. In the present study, we determined if the P2X(3) receptor (P2X(3)R) was associated with altered mechanical sensitivity of the whisker pad skin following complete Freund's adjuvant (CFA) injection into the lower lip. Mice with local inflammation induced by CFA injection into the lower lip demonstrated significant mechanical allodynia of whisker pad skin. The mechanical allodynia was reversed by P2X(3)R antagonist, A-317491 administration into whisker pad skin. The number of P2X(3)R and calcitonin gene-related peptide (CGRP) positive trigeminal ganglion (TG) neurons that innervates the whisker pad skin and lower lip was increased after CFA injection into the lower lip. CGRP protein expression in TG ipsilateral to CFA injection was also significantly greater than that of the saline-injected mice. The present findings suggest that induced CGRP by local inflammation in the lower lip increases P2X(3)R in TG neurons, the increased P2X(3)Rs are involved in the sensitization of primary afferent neurons in the whisker pad skin. This P2X(3)R overexpression may underlie ectopic mechanical allodynia in the whisker pad skin after CFA injection into the lower lip.

The use of easily debondable orthodontic adhesives with ceramic brackets.

We experimentally produced an easily debondable orthodontic adhesive (EDA) containing heat-expandable microcapsules. The purpose of this in vitro study was to evaluate the best debondable condition when EDA was used for ceramic brackets. Shear bond strengths were measured before and after heating and were compared statistically. Temperatures of the bracket base and pulp wall were also examined during heating. Bond strengths of EDA containing 30 wt% and 40 wt% heat-expandable microcapsules were 13.4 and 12.9 MPa, respectively and decreased significantly to 3.8 and 3.7 MPa, respectively, after heating. The temperature of the pulp wall increased 1.8-3.6°C after heating, less than that required to induce pulp damage. Based on the results, we conclude that heating for 8 s during debonding of ceramic brackets bonded using EDA containing 40 wt% heat-expandable microcapsules is the most effective and safest method for the enamel and pulp.